A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.

Automated summary

In this study, genetic analysis identified risk loci associated with basal cell carcinoma and squamous cell carcinoma. These risk loci are related to cancer development and progression, pigmentation, cardiometabolic factors, immune regulation, and HIV-1 viral load modulation. The study also proposed an optimized polygenic risk score for effective risk stratification of keratinocyte cancer.